Cancer Pharmacogenetics: perspective on newly discovered and implemented predictive biomarkers

Abstract

Implementation of pharmacogenetics (PGx) in the clinical practice of cancer therapy is one of the goals for a precision medicine. For some anticancer drugs (fluoropyrimidines and irinotecan) precise recommendations by regulatory agencies are available. However, in the future, implementation of PGx in clinical practice should also consider the anticancer drugs without available pharmacogenetic guidelines and the increasingly important role of rare PGx variants. To overcome barriers to PGx implementation we need to focus on pharmacogenetic test clinical utility by adopting a panel-based approach and sensitize both physician and patients to the therapeutic value of pharmacogenetic tests. Impact statementImplementation of Pharmacogenetics in Oncology is mandatory for precision medicine. Validated pharmacogenetic biomarkers require a pre-therapeutic screening, while the contribute of less validated and rare variants, of polytherapeutic and polygenic effect on patient's phenotype are becoming increasingly important.

Cardiotoxicity and pharmacogenetics of doxorubicin in black Zimbabwean breast cancer patients

“…In this study we could not verify clinical risk factors to be significant risk factors for developing DIC, of which previous studies have identified hypertension, female sex, age, cumulative anthracycline dose, as risk factors for DIC 3,14,27 . It may be possible that the small sample size in our study could have reduced the statistical power to demonstrate the significance of association of the clinical risk factors with DIC 12,[28][29][30][31][32][33] If we considered doxorubicin cumulative dose, we observe that there was no clear association between cumulative doxorubicin dose and cardiotoxicity (p = 0.357), which is not as expected 11,12,18,[34][35][36][37][38] . However, the high frequency (60.7%) of the cardioprotective variant could have influenced this dose relationship in our study.…”

Comparison of pharmacogenomic information for drug approvals provided by the national regulatory agencies in Korea, Europe, Japan, and the United States

“…Among the drugs for which pharmacogenomic information is mentioned, antineoplastic agents most commonly required a biomarker test. The importance of pharmacogenomic information in cancer treatment is well known because many anticancer drugs have narrow therapeutic ranges, and patients’ genetic background can have an effect on the pharmacokinetics of anticancer drugs ( Roncato et al, 2021 ). In addition, it has been revealed that targeted agents can be used as therapeutic options in addition to commonly used cytotoxic agents based on specific genetic mutations in various cancers including breast cancer, lung cancer, colorectal cancer, and melanoma ( Flaherty et al, 2010 ; Zhou et al, 2011 ; Yang et al, 2012 ; Roengvoraphoj et al, 2013 ).…”

“…Pharmacogenomics can facilitate the development of safe and effective drug therapy for individual patients by enabling appropriate drug selection and dose adjustment ( Relling and Evans, 2015 ). Pharmacogenomics has developed rapidly over the past 20 years, consequently promoting the realization of “personalized medicine” in healthcare ( Roncato et al, 2021 ).…”

An Integrated Pharmacological Counselling Approach to Guide Decision-Making in the Treatment with CDK4/6 Inhibitors for Metastatic Breast Cancer

“…CDKis have been introduced into clinical practice relatively recently, and there are currently little data on the potential use of pharmacogenetics to optimize their prescription. However, we have learned from other better studied gene-drug interactions such as DPYD -fluoropyrimidines, CYP2D6 -tamoxifen, TPMT/NUDT15 -thiopurines, and UGT1A1 -irinotecan ( Roncato et al, 2021 ), that genetic variability in ADME-related genes may be predictive of plasmatic drug exposure and clinical outcome. Similar exploratory results are available for some oral kinase inhibitors (KIs) as imatinib ( Gardner et al, 2006 ), gefitinib ( Li et al, 2007 ), sunitinib ( Diekstra et al, 2014 ), and the selective estrogen modulator tamoxifen ( Baxter et al, 2014 ) Therefore, it is tempting to hypothesize that similar effects could be observed for CDKis, but dedicated studies are needed.…”